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Science 23 March 2001:
Vol. 291. no. 5512, pp. 2364 - 2369
DOI: 10.1126/science.291.5512.2364

Review

Intracellular Functions of N-Linked Glycans

Ari Helenius,1* and Markus Aebi2

N-linked oligosaccharides arise when blocks of 14 sugars are added cotranslationally to newly synthesized polypeptides in the endoplasmic reticulum (ER). These glycans are then subjected to extensive modification as the glycoproteins mature and move through the ER via the Golgi complex to their final destinations inside and outside the cell. In the ER and in the early secretory pathway, where the repertoire of oligosaccharide structures is still rather small, the glycans play a pivotal role in protein folding, oligomerization, quality control, sorting, and transport. They are used as universal "tags" that allow specific lectins and modifying enzymes to establish order among the diversity of maturing glycoproteins. In the Golgi complex, the glycans acquire more complex structures and a new set of functions. The division of synthesis and processing between the ER and the Golgi complex represents an evolutionary adaptation that allows efficient exploitation of the potential of oligosaccharides.

1 Institute of Biochemistry,
2 Institute of Microbiology, Eidgenössische Technische Hochschule Zürich, Universitätstrasse 16, CH-8092 Zürich, Switzerland.
*   To whom correspondence should be addressed.


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A New Type of Non-Ca2+-buffering Apo(a)-based Fluorescent Indicator for Intraluminal Ca2+ in the Endoplasmic Reticulum.
K. Osibow, R. Malli, G. M. Kostner, and W. F. Graier (2006)
J. Biol. Chem. 281, 5017-5025
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Cytokine Response and Survival of Mice Immunized with an Adenovirus Expressing Bacillus anthracis Protective Antigen Domain 4.
M. J. McConnell, P. C. Hanna, and M. J. Imperiale (2006)
Infect. Immun. 74, 1009-1015
   Abstract »    Full Text »    PDF »
Inositol Deacylation by Bst1p Is Required for the Quality Control of Glycosylphosphatidylinositol-anchored Proteins.
M. Fujita, T. Yoko-o, and Y. Jigami (2006)
Mol. Biol. Cell 17, 834-850
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Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties.
E. Cancellotti, F. Wiseman, N. L. Tuzi, H. Baybutt, P. Monaghan, L. Aitchison, J. Simpson, and J. C. Manson (2005)
J. Biol. Chem. 280, 42909-42918
   Abstract »    Full Text »    PDF »
Carbohydrate-binding Agents Cause Deletions of Highly Conserved Glycosylation Sites in HIV GP120: A NEW THERAPEUTIC CONCEPT TO HIT THE ACHILLES HEEL OF HIV.
J. Balzarini, K. Van Laethem, S. Hatse, M. Froeyen, W. Peumans, E. Van Damme, and D. Schols (2005)
J. Biol. Chem. 280, 41005-41014
   Abstract »    Full Text »    PDF »
Endoplasmic Reticulum Glucosidase II Is Required for Pathogenicity of Ustilago maydis.
J. Schirawski, H. U. Bohnert, G. Steinberg, K. Snetselaar, L. Adamikowa, and R. Kahmann (2005)
PLANT CELL 17, 3532-3543
   Abstract »    Full Text »    PDF »
Sugar-binding Properties of VIP36, an Intracellular Animal Lectin Operating as a Cargo Receptor.
Y. Kamiya, Y. Yamaguchi, N. Takahashi, Y. Arata, K.-i. Kasai, Y. Ihara, I. Matsuo, Y. Ito, K. Yamamoto, and K. Kato (2005)
J. Biol. Chem. 280, 37178-37182
   Abstract »    Full Text »    PDF »
Role of N-Linked Glycans on Bunyamwera Virus Glycoproteins in Intracellular Trafficking, Protein Folding, and Virus Infectivity.
X. Shi, K. Brauburger, and R. M. Elliott (2005)
J. Virol. 79, 13725-13734
   Abstract »    Full Text »    PDF »
Nuclear Pore Complex Function in Saccharomyces cerevisiae Is Influenced by Glycosylation of the Transmembrane Nucleoporin Pom152p.
K. D. Belanger, A. Gupta, K. M. MacDonald, C. M. Ott, C. A. Hodge, C. M. Cole, and L. I. Davis (2005)
Genetics 171, 935-947
   Abstract »    Full Text »    PDF »
Identification of the hydrophobic glycoproteins of Caenorhabditis elegans.
X. Fan, Y.-M. She, R. D. Bagshaw, J. W. Callahan, H. Schachter, and D. J. Mahuran (2005)
Glycobiology 15, 952-964
   Abstract »    Full Text »    PDF »
Imino sugar inhibitors for treating the lysosomal glycosphingolipidoses.
T. D. Butters, R. A. Dwek, and F. M. Platt (2005)
Glycobiology 15, 43R-52R
   Abstract »    Full Text »    PDF »
Dominant Negative Mechanism Underlies Autosomal Dominant Stargardt-like Macular Dystrophy Linked to Mutations in ELOVL4.
C. Grayson and R. S. Molday (2005)
J. Biol. Chem. 280, 32521-32530
   Abstract »    Full Text »    PDF »
Key Golgi Factors for Structural and Functional Maturation of Bunyamwera Virus.
R. R. Novoa, G. Calderita, P. Cabezas, R. M. Elliott, and C. Risco (2005)
J. Virol. 79, 10852-10863
   Abstract »    Full Text »    PDF »
Glycosylation of Eag1 (Kv10.1) Potassium Channels: INTRACELLULAR TRAFFICKING AND FUNCTIONAL CONSEQUENCES.
J. Napp, F. Monje, W. Stuhmer, and L. A. Pardo (2005)
J. Biol. Chem. 280, 29506-29512
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Energetics of Substrate Binding and Catalysis by Class 1 (Glycosylhydrolase Family 47) {alpha}-Mannosidases Involved in N-Glycan Processing and Endoplasmic Reticulum Quality Control.
K. Karaveg and K. W. Moremen (2005)
J. Biol. Chem. 280, 29837-29848
   Abstract »    Full Text »    PDF »
RECK-Mediated Suppression of Tumor Cell Invasion Is Regulated by Glycosylation in Human Tumor Cell Lines.
S. Simizu, S. Takagi, Y. Tamura, and H. Osada (2005)
Cancer Res. 65, 7455-7461
   Abstract »    Full Text »    PDF »
Recombinant Pharmaceuticals from Plants: The Plant Endomembrane System as Bioreactor.
A. Vitale and E. Pedrazzini (2005)
Mol. Interv. 5, 216-225
   Abstract »    Full Text »    PDF »
A Cellular Deficiency of Gangliosides Causes Hypersensitivity to Clostridium perfringens Phospholipase C.
M. Flores-Diaz, A. Alape-Giron, G. Clark, B. Catimel, Y. Hirabayashi, E. Nice, J.-M. Gutierrez, R. Titball, and M. Thelestam (2005)
J. Biol. Chem. 280, 26680-26689
   Abstract »    Full Text »    PDF »



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